DNA methylation of the KLK8 gene in depression symptomatology.
DNA methylation of the KLK8 gene in depression symptomatology.
复制标题
抑郁症症状学中KLK8基因的DNA甲基化。
DOI：
10.1186/s13148-021-01184-5
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发表时间：
2021-10-29
影响因子：
5.7
通讯作者：
Staunstrup NH
中科院分区：
文献类型：
--
作者：
Starnawska A;Bukowski L;Chernomorchenko A;Elfving B;Müller HK;van den Oord E;Aberg K;Guintivano J;Grove J;Mors O;Børglum AD;Nielsen AL;Qvist P;Staunstrup NH
抑郁症是一种常见的，复杂的，使人衰弱的精神障碍，估计在社会中诊断不足，治疗不足。抑郁症的易感性受到遗传和环境风险因素的影响，这两个因素都能够影响DNA甲基化（DNAm）。因此，许多研究已经研究了这种疾病的DNAm特征。最近，单卵双胞胎的表观基因组关联研究确定了KLK 8（neuropsin）启动子区域的DNAm状态与抑郁症的严重程度之间的关联。在这项研究中，我们的目的是调查：（i）如果通过焦磷酸测序定量的KLK 8启动子中两个CpG位点处的血液DNAm水平与独立临床组群中的抑郁症发病学和抑郁症诊断相关，以及（ii）如果KLK 8 DNAm水平与四个独立甲基化组群中的抑郁症、产后抑郁症和抑郁症发病学相关，通过MBD-seq或450 k甲基化阵列定量血液和脑DNAm。KLK 8中的DNA m水平在抑郁症病例和对照组之间没有显著差异，并且在多重测试校正后与任何抑郁症行为学评分都没有显著相关（KLK 8 CpG 1的最小p值= 0.12，用于“抑郁情绪”，CpG 2的最小p值= 0.03，用于“与其他人失去自信”）。然而，对从四个甲基化组群收集的KLK 8启动子DNAm水平与抑郁症相关表型之间的联系的研究确定了抑郁症的严重程度与七个CpG位点处的血液DNAm水平之间的显著关联（p值< 0.05）。我们的研究结果表明，血液中KLK 8启动子区DNAm水平的变化与抑郁症症状的严重程度有关，但与抑郁症诊断无关。在线版本包含补充材料，可通过10.1186/s13148-021-01184-5获得。
Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for ‘Depressed mood,’ and for CpG2 = 0.03 for ‘Loss of self-confidence with other people’). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis. The online version contains supplementary material available at 10.1186/s13148-021-01184-5.
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影响因子：
10.6
作者：
Dempster EL;Wong CC;Lester KJ;Burrage J;Gregory AM;Mill J;Eley TC
通讯作者：
Eley TC
影响因子：
3.7
作者：
Aberg, Karolina A.;Chan, Robin F.;van den Oord, Edwin J. C. G.
通讯作者：
van den Oord, Edwin J. C. G.
影响因子：
11
作者：
Badenhop, R;Moses, MJ;Schofield, PR
通讯作者：
Schofield, PR
影响因子：
12.3
作者：
Gaunt TR;Shihab HA;Hemani G;Min JL;Woodward G;Lyttleton O;Zheng J;Duggirala A;McArdle WL;Ho K;Ring SM;Evans DM;Davey Smith G;Relton CL
通讯作者：
Relton CL
影响因子：
10.5
作者：
Farmer, A;Harris, T;McGuffin, P
通讯作者：
McGuffin, P